血卟啉单乙醚铜钠盐对~(60)Co辐射及正常小鼠造血系统的作用

目的探讨血卟啉单乙醚铜钠盐（HECu）对60Co辐射小鼠骨髓造血系统的影响，以期寻找再生障碍性贫血治疗药物。方法将昆明种正常小鼠，用60Coγ射线7.0Gy一次性全身照射为动物模型，通过对外周血血象的观察及骨髓造血干细胞的检测，研究HECu对60Co辐射小鼠及正常小鼠的血液系统的影响。结果HECu能升高60Co辐射小鼠的外周血白细胞计数，促进60Co辐射小鼠和正常小鼠的造血干细胞向红系转化。结论HECu对60Co辐射及正常小鼠的造血促进作用优于促粒细胞生长因子（G-CSF），以HECu为先导化合物值得进一步研究。     

再生障碍性贫血造血组织中瘦素水平分析

目的通过对再生障碍性贫血（再障）患者骨髓液及外周血瘦素水平的测定，探讨再障状态下骨髓造血微环境异常与瘦素的关系。方法按正常人（n=6）、再障（n=30）、急性白血病（n=20）及营养不良性贫血（n=20）分为四组，每位受试者均抽取骨髓液、外周血，用放射免疫分析法分别测定其瘦素浓度。结果再障组骨髓液和外周血瘦素水平分别与正常人、急性白血病、营养不良性贫血组比较，差异均有统计学意义（P〈0．01），而其他三组的骨髓液及外周血瘦素水平两两比较差异均无统计学意义（P〉0．05）。贫血程度与瘦素浓度无相关性（P〉0．05），但骨髓液与外周血瘦素浓度呈正相关（P〈0．01）。结论再障骨髓液、外周血瘦素水平明显增高，可能与再障骨髓脂肪细胞明显增多，脂肪细胞分泌瘦素明显增多有关。     

自体外周血干细胞移植

骨髓移植（BMT）公认已成为根治许多血液病和一些实体瘤的有力甚至唯一武器[1～3]。外周血于细胞移植（PBST）是指采集循环血中造血干细胞，移植给经强烈化疗或联合全身放疗的患者，使之造血和免疫重建。外周血干细胞移植的优势较BMT，PBST优点（1）感染合并症低。外周血干细胞为较成熟的造血祖细胞，而骨髓中为多能干细胞。经过相同剂量的移植前预处理，PBST后白细胞下降至零的时间短，故感染率低，程度轻。（2）复发率低。自体外周血干细胞PBST在患者经强烈化疗后采集，无或极少被肿瘤细胞污染，较骨髓常污染的自体BMT，移植后…     

昆布多糖对大鼠骨髓巨噬细胞生物活性的影响

目的研究昆布多糖对大鼠骨髓巨噬细胞生物活性的影响。方法制备并体外培养大鼠骨髓造血干／祖细胞、巨噬细胞;制备昆布多糖作用后的骨髓巨噬细胞条件培养液,测定培养液中造血生长因子促红细胞生成素（EP0）、粒-巨噬细胞集落刺激因子（GM—CSF）、白细胞介素-3（IL-3）表达及活性;测定昆布多糖条件培养液作用后造血祖细胞的集落产率。结果经昆布多糖诱导的骨髓巨噬细胞培养上清液可显著提高骨髓造血祖细胞的集落产率;经昆布多糖诱导后,骨髓巨噬细胞的EPO、GM—CSF和IL-3的表达增高。结论昆布多糖可刺激骨髓巨噬细胞造血因子表达增高,从而促进髓系多向性造血祖细胞（CFU—Mix）、红系祖细胞（CFU—E）、粒-单系造血祖细胞（CFU-GM）的增殖分化。     

外周血单纯性白细胞减少68例骨髓检查分析

目的 了解外周血单纯性白细胞减少患者骨髓检查的情况.方法 对2004年7月-2010年6月来我院就诊的68例单纯性白细胞减少的患者行骨髓穿刺术,涂片作瑞氏染色和组织化学染色,显微镜分类检查.结果 68例外周血单纯性白细胞减少患者,骨髓镜检无特殊改变8例（11.7%）,有异常改变60例（88.3%）,其中造血功能低下19例（27.9%）,感染性骨髓像15例（22.1%）,粒系成熟障碍17例（25.0%）,符合粒细胞减少症3例（4.4%）,骨髓增生异常综合症伴原始粒细胞增多2例（2.9%）,急性非淋巴细胞性白血病4例（5.9%）.结论 外周血单纯性白细胞减少与骨髓造血功能低下、恶性血液病有一定的关系,应引起高度重视.对于不明原因的外周血单纯性白细胞减少患者宜早行骨髓检查,明确病因.     

骨髓间充质干细胞生物学特性及其多向分化潜能的理论基础和机制

骨髓分为造血和基质两大系统，前者包括造血干细胞和各阶段血细胞；后者指骨髓腔内为造血系统提供结构和功能支持的结缔组织。因此，正常骨髓至少存在两种干细胞：骨髓造血干细胞（HSCs）和骨髓基质干细胞（MSCs）。后者以往被统称为骨髓基质细胞（BMSCs）。骨髓基质干细胞是近年才被确认的成体干细胞。长期以来，BMSCs一直被认为是骨髓中的造血结构性和功能性支持细胞，为造血干细胞的定居、自我更新和分化提供场所。后发现这些细胞易于在塑料瓶／皿表面贴壁生长，     

人工合成成骨生长肽对正常小鼠造血的促进作用和体外造血活性测定

目的　通过观察sOGP在体内的促造血活性和体外促进造血祖细胞增殖的作用 ,初步探索sOGP促造血活性的作用环节及机制。方法　正常小鼠连续 14d皮下注射sOGP ,观察外周血象、骨髓有核细胞数及骨髓有核细胞分类计数的变化 ;又应用离体骨髓细胞培养方法观察sOGP对正常小鼠和人骨髓粒系祖细胞集落形成的影响。结果　sOGP能升高正常小鼠骨髓有核细胞数和外周血白细胞数分别为2 0 %和 40 % ,红细胞和血小板也有增加趋势 ,骨髓细胞增生较空白对照组活跃 ,粒系增生较明显。体外CFU G集落培养实验进一步证实了sOGP具有直接刺激小鼠和人骨髓粒系祖细胞增殖的作用 ,1× 10 -14 mol·L-1浓度时已有明显的效果 ,sOGP和阳性对照药rhG CSF在相近浓度时效果相接近。结论　sOGP可能具有促进小鼠骨髓全系细胞增生的作用 ,以促进粒系造血为主 ,其机制可能是直接作用于造血干 /祖细胞或改善造血微环境促进造血 ,提示sOGP在促进放 /化疗患者造血功能恢复等方面潜在的应用价值     

重组人粒细胞—巨噬细胞集落刺激因子的临床研究进展

本文着重从骨髓发育异常综合症，骨髓移植，外周血造血干细胞移植，恶性肿瘤放疗和化疗引起的白细胞减少症和白血病等方面介绍了重组人粒细胞－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）近些年的临床研究进展情况。     

生白饮对钴60照射小鼠造血系统损伤保护作用

目的：研究生白饮对^60Coγ射线照射小鼠造血系统损伤保护作用。方法：连续动态观察生白饮对小鼠经^60Coγ射线照射后7，14，21d外周血白细胞、骨髓有核细胞数、淋巴细胞转化指数、网织红细胞以及细胞肿瘤因子（TNF）、白细胞介素-6（IL6）活性的影响。结果：照射损伤后小鼠外周血白细胞、网织红细胞、骨髓有核细胞数明显减少，淋巴细胞转化指数下降。TNF、IL-6活性降低。生白饮可促进上述各造血指标的恢复及升高（P〈0．05或P〈0．01）。结论：生白饮对照射损伤小鼠造血系统具有保护作用。     

内科疾病处方用药解析（47）

5血液系统疾病 5.7.2慢性髓细胞白血病慢性髓细胞白血病（CML）是一种发生在多能造血干细胞上的恶性骨髓增生性疾病（获得性造血干细胞恶性克隆性疾病）,主要涉及髓系。外周血粒细胞显著增多并有不成熟性,在受累的细胞系中,     

Effects of neopterin on the hematopoietic microenvironment of senescence-accelerated mice (SAM)

The pteridine neopterin (NP) is produced by monocytes and is known to be a useful marker of immunological activation, although, it remains elusive whether neopterin itself exhibits biological functions. Recently, we found that NP stimulates hematopoietic cell proliferation and differentiation by activating bone marrow stromal cell function. In order to elucidate the biological effect of NP on stromal cells, its effects on hematopoiesis was determined in the mouse model of age-related stromal impairment, senescence-accelerated mice (SAMs). An intraperitoneal administration of NP increased the number of peripheral leukocytes and CFU-GM in the bone marrow and spleen of young SAMs, however, no increase of CFU-GM in old SAMs (stromal impairment) was observed when compared with young SAMs. NP also increased the CFU-GM colony formation of bone marrow and spleen cells from young SAMs in a soft agar culture system, but it did not enhance CFU-GM colony formation of cells from old SAMs cultured in this system. Treatment with NP induced the production of hematopoietic stimulating factors, including IL-6 and GM-CSF, by bone marrow stromal cells from young SAMs but stromal cells from old SAMs did not respond to NP stimulation. Further studies will be required to clarify the mechanism by which NP stimulates the production of hematopoietic growth factors from stromal cells, the results of this study indicate that NP is a potent hematopoietic regulatory factor by activating stromal cell function(s).     

Evaluation of myelotoxicity in cotton rats (Sigmodon hispidus) exposed to environmental contaminants. I. In vitro bone-marrow progenitor culture

Bone marrow is extremely sensitive to toxicants, and in vitro culture of bone-marrow progenitor cells has been shown to be a sensitive indicator of bone-marrow injury in laboratory rodents. The ability of a bone-marrow progenitor cell assay to detect myelotoxicity in a wild rodent model (cotton rat, Sigmodon hispidus) that inhabits many contaminated ecosystems in the southern United States was examined. Responsiveness of progenitor cells to recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and cotton rat lung-conditioned medium (LCM) was determined to optimize culture conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexamethasone (500 microg/kg) over a 5-d period. Administration of a high dose of cyclophosphamide caused nearly total suppression of colony formation of granulocyte-macrophage progenitor cells (CFU-GM). Marked histological changes in both the bone marrow and spleen were also observed in cotton rats treated with a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophosphamide- and dexamethasone-treated cotton rats was significantly suppressed compared to controls. The number of CFU-GM was consistently higher using LCM than recombinant murine GM-CSF. This reproducible, quantitative, in vitro bone-marrow progenitor cell culture system was a sensitive indicator of myelotoxicity in wild cotton rats and should be useful for monitoring chronic exposures to low levels of environmental toxicants in wild rodent populations.     

Evaluation Of Myelotoxicity In Cotton Rats (Sigmodon hispidus) Exposed To Environmental Contaminants. I. In Vitro Bone-Marrow Progenitor Culture

Bone marrow is extremely sensitive to toxicants, and in vitro culture of bone-marrow progenitor cells has been shown to be a sensitive indicator of bone-marrow injury in laboratory rodents. The ability of a bone-marrow progenitor cell assay to detect myelotoxicity in a wild rodent model (cotton rat, Sigmodon hispidus) that inhabits many contaminated ecosystems in the southern United States was examined. Responsiveness of progenitor cells to recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and cotton rat lung-conditioned medium (LCM) was determined to optimize culture conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexamethasone (500 µg/kg) over a 5-d period. Administration of a high dose of cyclophosphamide caused nearly total suppression of colony formation of granulocyte-macrophage progenitor cells (CFU-GM). Marked histological changes in both the bone marrow and spleen were also observed in cotton rats treated with a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophosphamide- and dexamethasone-treated cotton rats was significantly suppressed compared to controls. The number of CFU-GM was consistently higher using LCM than recombinant murine GM-CSF. This reproducible, quantitative, in vitro bone-marrow progenitor cell culture system was a sensitive indicator of myelotoxicity in wild cotton rats and should be useful for monitoring chronic exposures to low levels of environmental toxicants in wild rodent populations.     

沙纳唑合并γ射线对在体小鼠骨髓粒系造血祖细胞的影响

目的 :研究沙纳唑直接给药以及合并γ射线照射处理对在体小鼠骨髓粒系造血祖细胞 (CFU -GM )集落形成的影响。方法 :通过对小鼠骨髓CFU -GM培养的检测 ,观察从小鼠尾静脉注射不同剂量沙纳唑对小鼠造血系统的影响 ;并于不同放射剂量照射前30min从小鼠尾静脉注射不同剂量沙纳唑 ,观察沙纳唑合并γ射线照射处理对小鼠造血系统的影响。结果 :静脉注射沙纳唑对在体小鼠骨髓CFU -GM集落形成抑制作用较小 ;沙纳唑合并γ射线照射处理后对小鼠骨髓CFU -GM的抑制作用与单一放射照射处理结果相似。结论 :沙纳唑直接给药对在体小鼠骨髓CFU -GM无明显细胞毒性作用 ,合并放射照射处理对放射照射所致小鼠骨髓CFU -GM的抑制没有明显协同作用。     

巴西蘑菇多糖对造血干、祖细胞生成的影响

目的:探讨国产巴西蘑菇多糖对造血干、祖细胞生成的影响及其作用机制。方法:应用造血细胞培养技术、流式细胞仪(FACS)、逆转录多聚酶链反应(RT-PCR)观察药物对小鼠骨髓细胞及人脐血单个核细胞的影响。结果:经过巴西蘑菇多糖处理的动物,造血干细胞(CFU-S)、粒-单祖细胞(CFU-GM)、红系祖细胞(CFU-E)和纤维母细胞(CFU-F)各组数值明显上升,与对照组比较,P均<0.01;FACS检测显示,实验组CD33+细胞明显上升,在诱导的d 7达高峰;经RT-PCR检测结果表明,巴西蘑菇多糖诱导人脐血单个核细胞48 h后,粒单细胞克隆刺激因子(GM-CSF)mRNA的表达量是对照组的2.72倍。结论:巴西蘑菇多糖可促进造血干、祖细胞生成并可促进人脐血单个核细胞GM-CSF基因表达。     

地黄寡糖对SAMP8小鼠造血祖细胞增殖的作用

采用造血祖细胞体外克隆培养等实验血液学技术, 研究了地黄寡糖对快速老化模型P系小鼠(SAMP8)骨髓造血祖细胞增殖作用的影响. 结果表明地黄寡糖可促进SAMP8小鼠骨髓粒系巨噬系祖细胞, 早期和晚期红系祖细胞的增殖, 其脾细胞条件液也可使造血祖细胞克隆集落数明显增加, 地黄寡糖还可使其基质细胞层上粒系巨噬系祖细胞集落的产率明显增多. 提示地黄寡糖可能通过多种途径激活机体组织, 特别是造血微环境中的某些细胞, 促进其分泌多种造血生长因子而增强造血祖细胞的增殖.     

小鼠干细胞因子基因以脂质体介导转染脐血细胞

目的小鼠干细胞因子 (SCF)以脂质体介导转染脐血细胞并表达。方法采用PCR技术从 pRC/CMV(含SCFcDNA)中钓取SCFcDNA膜外段活性区 ,克隆入真核表达载体 pcDNA3 ,转染传 2代的脐血细胞 ;用RT PCR方法检测mRNA表达水平及通过协同刺激集落形成来检测转染细胞上清的生物活性。结果转染SCFcDNA的脐血细胞SCFmRNA水平表达量高于对照组 ,其细胞培养上清协同GM CSF刺激骨髓细胞形成集落数比GM CSF单独作用高两倍左右。结论脂质体介导质粒载体转染培养富集的脐血细胞并表达 ,且转染上清具有生物学活性 ,为进一步研究转染基因的表达特性及持续时间提供依据。     

微载体—基质细胞造血模型中小鼠骨髓细胞c—kit基因的表达

目的：检测小鼠原始造血细胞c-kit基因表达以评价体外模拟骨髓造血微环境。方法：建立微载体－基质细胞体外造血模型。根据已发表的小鼠c-kit基因序列设计引物，采用RT－PCR方法检测c-kit mRNA水平，并测定祖细胞集落产率。结果：小鼠骨髓造血细胞2周培养实验显示，粒系－巨噬系造血祖细胞集落产率（CFU－GM／10^5）：模型组比液体悬浮培养和单纯微载体基质细胞培养对照组集落产率之总和高2．1倍（t=2.869,P＜0．05）；原始造血细胞的c-kit基因表达水平（OD比率）：模型组比两个对照组之总和高3．1倍（t=2.858,P＜0．05）。结论：在没有外加细胞因子的条件下，微载体－基质细胞造血模型可抑造血干、祖细胞过度分化与耗竭，维持其c-kit mRNA较高的表达水平。     

Stimulation of myelopoiesis in Listeria monocytogenes-infected mice by an aggregated polymer isolated from Aspergillus oryzae

In this work, we investigated the effects of the proteic aggregated polymer of magnesium ammonium phospholinoleate-palmitoleate anhydride (MAPA) isolated from Aspergillus oryzae on the growth and differentiation of bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in Listeriamonocytogenes-infected mice. A significant reduction in the CFU-GM number was observed in the initial phase of infection with a sublethal dose of Listeria. Treatment of mice with 0.5, 2.0 and 5.0 mg/kg MAPA for 7 days prior to infection significantly stimulated myelopoiesis in a dose-dependent manner. Moreover, treatment with 0.5 and 5.0 mg/kg MAPA resulted in 30% and 40% cures of mice lethally infected with Listeria, respectively. MAPA added directly to the culture dishes hardly affected colony formation by bone marrow cells, suggesting an indirect effect ofthis compound on myelopoiesis in vivo. In summary, the data show that MAPA can modulate the CFU-GM generation and antibacterial resistance in listeriosis. As the ability of hematopoietic tissues to produce phagocytes is of particular significance to mediate resistance to Listeria, the promotion of bone marrow CFU-GM by MAPA may contribute to a rapid restoration of phagocyte numbers in infected sites, thus mitigating the course of infection.     

Preclinical in vitro evaluation of hematotoxicity of the cisplatin-procaine complex DPR

We evaluated in vitro the inhibitory effect of cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR) on colony formation by granulocyte/macrophage (CFU-GM) peripheral blood progenitor cells, representing a method to quantitate the toxicity of drugs to the hematopoietic system, and human leukemic cell lines. The results were compared with those obtained exposing cells to cisplatin and carboplatin. Our data showed that while DPR had a significantly better cytotoxic activity than cisplatin and carboplatin against HL60 and K562, and than carboplatin against Molt 4 cells, it showed 12 and 43 times less inhibitory effect on CFU-GM than cisplatin and carboplatin, respectively. These results suggest that the myelosuppressive activity of DPR could be lower than that of cisplatin and carboplatin, and, furthermore, that leukemic cells represent a preferential target for its cytotoxic activity compared to normal committed hemopoietic progenitor cells. All our results speak in favor of a better therapeutic index for DPR than for the other platinum compounds considered here.